Mass spectrometry is a well-known analytical technique for the accurate determination of molecular weights, identification of chemical structures, determination of the composition of mixtures, and qualitative elemental analysis. A mass spectrometer generates ions of sample molecules under investigation, separates the ions according to their mass-to-charge ratio, and measures the abundance of each ion. The ion mass is expressed in Daltons (Da), or atomic mass units and the ion charge is the charge on the ion in terms of the number of electron charges.
Time-of-flight (TOF) mass spectrometers separate ions according to their mass-to-charge ratio by measuring the time it takes generated ions to travel to a detector. The flight time of an ion accelerated by a given electric potential is proportional to its mass-to-charge ratio. Thus, the TOF of an ion is a function of its mass-to-charge ratio and is approximately proportional to the square root of the mass-to-charge ratio. TOF mass spectrometers are relatively simple, inexpensive, and have a virtually unlimited mass-to-charge ratio range. Since other types of mass spectrometers are not capable of detecting the ions of large organic molecules, TOF mass spectrometers are very beneficial in this particular area of use. However, the earliest TOF mass spectrometers, see Stephens, W. E., Phys. Rev., vol. 69, p. 691, 1946 and U.S. Pat. No. 2,612,607, had poor mass resolution (i.e., the ability to differentiate ions having almost the same mass at different flight times).
Ideally, all ions of a particular mass have the same charge and arrive at the detector at the same time, with the lightest ions arriving first, followed by ions progressively increasing in mass. In practice, ions of equal mass and charge do not arrive at the detector simultaneously due to the initial temporal, spatial, and kinetic energy distributions of generated ions. These distributions may be inherent to the method used to generate the ions or may be generated by collisions during the extraction of ions from the source region. These initial distribution factors lead to a broadening of the mass spectral peaks, which leads to limits in the resolving power of the TOF mass spectrometer.
TOF mass spectrometers were first designed and commercialized in late 1940s and mid 1950s. Major improvements in TOF mass spectrometers were made by William C. Wiley and I. H. McLaren. These instruments are typically designed by seeking a set of design parameters that cause the first and/or second partial derivative of the time-of-flight with respect to the initial ion velocity identically to be zero. See U.S. Pat. No. 2,685,035 and Wiley, W. C. and McLaren, I. H., Rev. Sci. Instrumen., vol. 26, pp. 1150–57, 1955. These inventions resulted in the improved mass resolution by the use of a time-lag focusing scheme that corrected for the initial spatial and kinetic energy (velocity) distributions of the ions. More recent improvements to TOF mass spectrometers to reduce temporal and spatial distributions include energy focusing by the use of ion reflectors. See U.S. Pat. No. 4,731,532 and U.S. Pat. No. 6,013,913.
To date, all ion-focusing schemes have assumed that the best way to deal with a large spread in initial ion energy distribution is to reduce the energy spread in the extraction region. See Gohl, W., et al., Int. J. Mass Spectrom. Ion Phys., vol 48, pp. 411–14, 1983. The prime example of this is the commonly used delay extraction technique, which was developed to specifically narrow the energy distribution of the ions. Other methods to narrow the initial ion energy distribution have included monotonically increasing the extraction potential. See U.S. Pat. No. 5,969,348. None of these methods have allowed for the development of a compact TOF mass spectrometer that retains the high mass resolution of full sized instruments.
Even though these TOF mass spectrometer methods have increased mass resolution over a broad range of ion masses, greater improvements are warranted. There is a growing demand for more compact, high mass resolution, broad mass spectrum mass spectrometers, especially for applications such as the detection of biologically important molecules in extraterrestrial environments for proteomics, rapid identification of biological agents, or the detection of infectious disease contamination in hospitals. Therefore, it is an object of this invention is to provide a method and design for a TOF mass spectrometer that has greater mass resolution over a broad range of ion masses. An additional object of this invention is to provide a method and design for decreasing the physical size of the TOF mass spectrometer while providing high mass resolution over a broad range of ion masses.